The overall objective of the research is the study of a bone resorptive protein (BRP) and its relationship to osteolytic neoplastic diseases and hypercalcemia. Particular emphasis will be placed on the characterization of BRP, which we have isolated from human cancer ascites fluid. The studies will also include investigations on the biological mechanism of action of OAF. We have recently developed a specific immunoassay for BRP and are now establishing the identity of the ascites protein with that of lymphocyte-derived BRP, determining its cell of origin, and evaluating the levels of BRP in patients with osteolytic lesions of the skeleton and cancer-related hypercalcemia. Recent studies on the mechanism of action of the bone resorptive protein demonstrate that this protein stimulates matrix resorption in vitro and also mobilizes calcium in vivo. Moreover, the protein, on the basis of in vitro studies, appears to act through the stimulation of prostaglandin synthesis. (W)